Efficacy and safety of IL-6 inhibitors for polymyalgia rheumatica: a meta-analysis of randomized controlled trials
Eficácia e segurança dos inibidores de IL-6 para polimialgia reumática: uma metanálise de estudos clínicos randomizados
Alexandre Wagner Silva De Souza Beatriz Austregésilo De A. De H. Morais; Maria Luiza Rodrigues Defante; Vanio Antunes Do Livramento Junior; Otavio Cosendey Martins; Mariana De Moura De Souza; Beatriz Ximenes Mendes; Vitoria Martins Prizão
Abstract
Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disease, common in older adults, characterized by fatigue, morning stiffness, and pain in the neck, shoulders, and hip girdle. Its pathophysiology is believed to involve abnormal interleukin (IL)-6 activity. Although glucocorticoids are the standard treatment, frequent relapses and long-term adverse effects pose challenges. IL-6 inhibitors may offer an alternative, but their efficacy in isolated PMR, unlike in giant cell arteritis, remains unclear. The present review sought to evaluate the efficacy and safety of IL-6 inhibitors (tocilizumab, sarilumab) combined with glucocorticoids versus glucocorticoids alone in PMR. A systematic review was conducted in the PubMed, Embase, and Cochrane databases to identify randomized controlled trials (RCTs). The primary outcome was the SF-36 Physical Component Score. Secondary outcomes included adverse events, treatment discontinuation, and evaluator global assessment via visual analogue scale (VAS). Analyses were performed in R 4.3.1, with odds ratios (OR) for binary and mean differences (MD) for continuous outcomes, all with 95% confidence intervals (CI). Heterogeneity was assessed using I². Four RCTs (n=358; IL-6 inhibitors=188; placebo=170) were included. IL-6 inhibitors significantly improved SF-36 scores (MD 4.75; CI 0.67 to 8.83; p=0.02). No significant differences were found in adverse events (OR 1.69; p=0.16), discontinuation rates (OR 0.80; p=0.723), or VAS scores (MD -6.51; CI -12.92 to -0.09). IL-6 inhibitors improved physical function without increasing adverse events, supporting their potential use as adjunctive therapy in PMR.
Keywords
Resumo
A polimialgia reumática (PMR) é uma doença reumática inflamatória comum em idosos, caracterizada por fadiga, rigidez matinal e dor em região cervical, cintura escapular e pélvica. Sua fisiopatologia parece envolver atividade anormal da interleucina-6 (IL-6). Embora os glicocorticoides sejam o tratamento padrão, recaídas frequentes e efeitos adversos em longo prazo representam desafios. Inibidores de IL-6 podem oferecer uma alternativa, mas sua eficácia em casos isolados de PMR, diferentemente da arterite de células gigantes, ainda é incerta. Este trabalho teve por objetivo avaliar a eficácia e segurança dos inibidores de IL-6 (tocilizumabe, sarilumabe) associados a glicocorticoides, em comparação ao uso isolado de glicocorticoides na PMR. Realizou-se uma revisão sistemática nas bases PubMed, Embase e Cochrane para identificar ensaios clínicos randomizados (ECRs). O desfecho primário foi o escore físico do SF-36. Desfechos secundários incluíram taxa de eventos adversos, descontinuação do tratamento e avaliação global do investigador por escala visual analógica (EVA). As análises foram realizadas no R 4.3.1, utilizando razão de chances (OR) para desfechos binários e diferença média (DM) para contínuos, com intervalos de confiança (IC) de 95%. A heterogeneidade foi avaliada com estatística I². Foram incluídos quatro ECRs (n = 358; IL-6i = 188; placebo = 170). Os inibidores de IL-6 melhoraram significativamente o escore físico do SF-36 (DM 4,75; IC 0,67-8,83; p = 0,02). Não houve diferenças significativas nos eventos adversos (OR 1,69; p = 0,16), descontinuações (OR 0,80; p = 0,723) ou EVA (DM -6,51; IC -12,92 a -0,09). Os inibidores de IL-6 melhoraram a função física sem aumento nos eventos adversos, sugerindo seu potencial como terapia adjuvante na PMR.
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Referências
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Submetido em:
01/07/2025
Aceito em:
17/07/2025
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